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Novel Methylation Patterns Predict Outcome in Uveal Melanoma

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Novel Methylation Patterns Predict Outcome in Uveal Melanoma Article Novel Methylation Patterns Predict Outcome in Uveal Melanoma Sarah Tadhg Ferrier 1 and Julia Valdemarin Burnier 1,2,3,* 1 Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, H4A 3J1; [email protected] 2 Experimental Pathology Unit, Department of Pathology, McGill University; Montreal, QC, Canada, H3A 0G4 3 Department of Oncology, McGill University; Montreal, QC, Canada, H3A 0G4 * Correspondence: [email protected] Table S1. Differentially methylated genes in the Pathways in Cancer KEGG pathway with a log FC ≥ 1.5. Average Average Log Fold Change Differentially Adjusted P Beta Beta ID Gene Name Species (High vs Low Methylated Probes Value Value, Value, Risk) Low High ABL proto-oncogene 1, non- ABL1 Homo sapiens cg13440206, −1.85238 1.39E−06 0.576589 0.259088 receptor tyrosine kinase(ABL1) cg02915920 −1.84042 8.03E−06 0.482846 0.192714 cg21195763 1.685721 3.13E−19 0.573548 0.83358 ADCY2 adenylate cyclase 2(ADCY2) Homo sapiens cg14116052 2.454448 4.3E−24 0.513149 0.885217 ADCY6 adenylate cyclase 6(ADCY6) Homo sapiens cg25196508 3.480923 2.9E−25 0.188362 0.792499 AKT serine/threonine kinase AKT1 Homo sapiens cg14116052 2.454448 4.3E−24 0.513149 0.885217 1(AKT1) bone morphogenetic protein BMP4 Homo sapiens cg08046044 1.527233 3.98E−06 0.049923 0.209543 4(BMP4) cg01873886 1.789942 2.55E−05 0.026254 0.1723 Life 2020, 10, x; doi: FOR PEER REVIEW www.mdpi.com/journal/life Life 2020, 10, x FOR PEER REVIEW 2 of 22 cyclin dependent kinase inhibitor CDKN1B Homo sapiens cg06197769 3.78761 1.9E−30 0.187364 0.82662 1B(CDKN1B) CTNNA3 catenin alpha 3(CTNNA3) Homo sapiens cg09538287 2.037243 5.62E−09 0.251955 0.539339 death associated protein kinase DAPK3 Homo sapiens cg22304239 1.939735 1.18E−13 3(DAPK3) endothelin receptor type EDNRB Homo sapiens cg18210860 2.815506 1.87E−14 0.444524 0.810551 B(EDNRB) cg24785726 3.163564 2.54E−15 0.080629 0.539854 cg23326536 3.195834 6.45E−17 0.071876 0.541248 cg13866767 3.463542 1.49E−19 0.28389 0.815008 endothelial PAS domain protein EPAS1 Homo sapiens cg21276379 1.824026 5.68E−14 0.186755 0.437118 1(EPAS1) cg17091312 2.112437 2.76E−23 ETS proto-oncogene 1, ETS1 Homo sapiens cg25244476 2.507626 9.92E−07 0.25583 0.602367 transcription factor(ETS1) FGF1 fibroblast growth factor 1(FGF1) Homo sapiens cg15371881 3.061708 4.38E−25 0.219393 0.69523 FZD6 frizzled class receptor 6(FZD6) Homo sapiens cg10929921 3.957203 3.22E−19 0.333365 0.912152 G protein subunit alpha GNA11 Homo sapiens cg02261780 2.268738 2.51E−16 0.353174 0.732472 11(GNA11) cg24366168 2.349167 6.69E−12 0.43427 0.894937 cg00168191 2.478771 1.2E−11 0.510916 0.876102 cg13527233 2.144414 1.19E−11 0.540858 0.863307 GNAI1 G protein subunit alpha i1(GNAI1) Homo sapiens cg05424060 1.904542 2.69E−07 GNB4 G protein subunit beta 4(GNB4) Homo sapiens cg01750654 1.647758 4.02E−11 0.594913 0.827501 cg03466124 1.862402 3.31E−08 0.108087 0.324521 Life 2020, 10, x FOR PEER REVIEW 3 of 22 G protein subunit gamma GNG11 Homo sapiens cg06439941 2.094159 1.67E−09 0.218242 0.565099 11(GNG11) cg08038054 2.335425 3.13E−11 0.069817 0.348166 cg02914800 3.14371 1.04E−14 0.10902 0.602134 glutathione S-transferase pi GSTP1 Homo sapiens cg22224704 2.261199 1.11E−08 0.19543 0.520111 1(GSTP1) cg11566244 3.087685 6.52E−12 0.134838 0.555003 insulin like growth factor 1 IGF1R Homo sapiens cg11852333 1.967845 3.57E−14 0.258781 0.568105 receptor(IGF1R) ITGA3 integrin subunit alpha 3(ITGA3) Homo sapiens cg12127162 1.833962 2.92E−16 0.254277 0.538208 ITGAV integrin subunit alpha V(ITGAV) Homo sapiens cg03192874 2.961775 2.21E−15 KRAS proto-oncogene, KRAS Homo sapiens cg23152216 2.293392 5.96E−27 0.470784 0.837552 GTPase(KRAS) lysophosphatidic acid receptor LPAR6 Homo sapiens cg03646329 2.221789 8.4E−09 0.105173 0.345011 6(LPAR6) mitogen-activated protein kinase MAPK8 Homo sapiens cg19612574 1.694113 4.14E−15 0.113088 0.332177 8(MAPK8) mitogen-activated protein kinase MAPK9 Homo sapiens cg09663237 2.203989 3.06E−06 0.584195 0.883176 9(MAPK9) MMP2 matrix metallopeptidase 2(MMP2) Homo sapiens cg00355286 1.518071 7.31E−10 0.183672 0.439098 platelet derived growth factor PDGFRA Homo sapiens cg02273436 1.911305 1.17E−06 0.160494 0.467324 receptor alpha(PDGFRA) phosphoinositide−3-kinase PIK3R1 Homo sapiens cg01251150 2.237358 1.26E−17 0.060815 0.28225 regulatory subunit 1(PIK3R1) Life 2020, 10, x FOR PEER REVIEW 4 of 22 pleckstrin homology and RhoGEF PLEKHG5 Homo sapiens cg07181374 1.727515 1.69E−17 domain containing G5(PLEKHG5) PML promyelocytic leukemia(PML) Homo sapiens cg01947066 1.959361 1.08E−06 peroxisome proliferator activated PPARD Homo sapiens cg26668919 2.934903 3.68E−17 receptor delta(PPARD) PRKCA protein kinase C alpha(PRKCA) Homo sapiens cg14121185 −2.67592 1.62E−20 0.874693 0.429846 cg05115424 1.608107 7.51E−10 0.081959 0.220044 cg09655520 1.820661 1.39E−09 0.166933 0.419827 phosphatase and tensin PTEN Homo sapiens cg26127345 1.535502 0.001508 0.429051 0.633389 homolog(PTEN) cg19358349 1.702888 0.000271 0.401807 0.644288 cg01228636 1.712449 0.000372 0.491384 0.734546 cg19634213 1.721931 0.00022 0.40649 0.663402 cg04616691 1.78722 0.000905 0.364272 0.561777 cg03236184 1.901193 7.83E−05 0.438936 0.706127 RARB retinoic acid receptor beta(RARB) Homo sapiens cg21902772 2.206659 9.56E−18 0.291665 0.708268 cg23518541 3.4762 1.05E−16 0.096579 0.60235 Ras association domain family RASSF1 Homo sapiens cg02930432 1.590468 2.75E−09 0.197452 0.462608 member 1(RASSF1) cg21418575 1.510304 9.39E−08 0.335072 0.572985 cg07130266 2.266083 3.24E−09 0.249514 0.57952 RB transcriptional corepressor RB1 Homo sapiens cg13221796 1.972518 2.27E−20 1(RB1) RXRB retinoid X receptor beta(RXRB) Homo sapiens cg07931652 1.523593 4.19E−17 0.524678 0.77896 Life 2020, 10, x FOR PEER REVIEW 5 of 22 solute carrier family 2 member SLC2A1 Homo sapiens cg22025263 2.001813 8.33E−11 0.510382 0.81735 1(SLC2A1) SMAD3 SMAD family member 3(SMAD3) Homo sapiens cg04809597 1.97252 1.92E−23 0.05713 0.252782 SUFU negative regulator of SUFU Homo sapiens cg09119776 1.824803 1.59E−16 0.068277 0.233147 hedgehog signaling(SUFU) transcription factor 7 like TCF7L1 Homo sapiens cg20693690 −1.5635 3.97E−07 0.533941 0.240248 1(TCF7L1) cg22834443 1.837207 1.9E−12 0.548775 0.843847 cg20693690 −1.5635 3.97E−07 0.533941 0.240248 transcription factor 7 like TCF7L2 Homo sapiens cg07168930 1.804367 1.5E−14 0.712649 0.911392 2(TCF7L2) cg03339956 2.395134 3.93E−26 0.218402 0.600015 transforming growth factor beta TGFB2 Homo sapiens cg11976166 −1.8673 2.93E−05 0.442588 0.167974 2(TGFB2) cg10484211 2.167142 1.63E−13 0.08019 0.33298 cg13285637 −1.8383 6.64E−05 0.424687 0.162007 cg06899755 −1.54824 0.000222 0.447125 0.173171 cg22021178 −1.50285 0.000406 0.359804 0.125219 Table S2. Differentially methylated genes in the Tumor Suppressors KEGG pathway with a log FC ≥ 1.5. Log Fold Change Average Average Differentially Adjusted P Gene Name Species (High vs Low Beta Value, Beta Value, Methylated Probes Value Risk) Low High Life 2020, 10, x FOR PEER REVIEW 6 of 22 ATM serine/threonine ATM Homo sapiens cg14761454 2.171709 5.33E−11 0.113337 0.410785 kinase(ATM) cyclin dependent kinase inhibitor CDKN1B Homo sapiens cg06197769 3.78761 1.9E−30 0.187364 0.82662 1B(CDKN1B) cyclin dependent kinase inhibitor CDKN1C Homo sapiens cg17265994 1.60087 5.24E−15 0.098808 0.272309 1C(CDKN1C) cg03143849 1.697443 4.88E−16 0.380944 0.710675 cyclin dependent kinase inhibitor CDKN2D Homo sapiens cg25685983 1.766552 7.18E−23 0.110149 0.323895 2D(CDKN2D) DAB2, clathrin adaptor DAB2 Homo sapiens cg12290311 3.117633 5.95E−21 0.09455 0.555251 protein(DAB2) death associated protein kinase DAPK3 Homo sapiens cg22304239 1.939735 1.18E−13 3(DAPK3) DIS3 like 3'−5' exoribonuclease DIS3L2 Homo sapiens cg14802771 2.279833 3.93E−17 0.193749 0.543178 2(DIS3L2) DLC1 Rho GTPase activating DLC1 Homo sapiens cg18792365 2.274905 5.82E−10 0.185786 0.565794 protein(DLC1) cg22045977 2.575186 2.44E−15 0.407574 0.828947 EFNA1 ephrin A1(EFNA1) Homo sapiens cg07207669 1.829389 7.93E−07 0.308278 0.606053 FES proto-oncogene, tyrosine FES Homo sapiens cg25647583 1.620561 1.83E−12 0.337424 0.613609 kinase(FES) cg26405020 1.775185 3.08E−16 0.103383 0.313802 cg09397246 1.7864 4.28E−11 0.038035 0.194971 hypoxia inducible factor 3 alpha HIF3A Homo sapiens cg12068280 2.287241 3.28E−19 0.23857 0.656095 subunit(HIF3A) Life 2020, 10, x FOR PEER REVIEW 7 of 22 hydroxyprostaglandin HPGD Homo sapiens cg03772063 2.169526 7.27E−13 0.544367 0.843968 dehydrogenase 15-(NAD)(HPGD) mutated in colorectal MCC Homo sapiens cg02528008 2.18208 3.41E−17 0.138006 0.447979 cancers(MCC) microtubule associated tumor MTUS1 Homo sapiens cg00121389 2.338386 4.67E−18 0.289024 0.711872 suppressor 1(MTUS1) cg01993952 3.183913 3.56E−18 0.331804 0.792952 cg23002008 3.231493 8.86E−18 0.394688 0.876206 cg12548824 3.485792 2.2E−25 0.250505 0.83362 cg18563140 3.558719 8.99E−23 PIN2/TERF1 interacting, PINX1 Homo sapiens cg26886855 2.717973 1.02E−10 telomerase inhibitor 1(PINX1) PML promyelocytic leukemia(PML) Homo sapiens cg01947066 1.959361 1.08E−06 PRKCD protein kinase C delta(PRKCD) Homo sapiens cg08170911 2.447478 8.68E−26 0.173984 0.533695 phosphatase and tensin PTEN Homo sapiens cg26127345 1.535502 0.001508 0.429051 0.633389 homolog(PTEN) cg19358349 1.702888 0.000271 0.401807 0.644288 cg01228636 1.712449 0.000372 0.491384 0.734546 cg19634213 1.721931 0.00022 0.40649 0.663402 cg04616691 1.78722 0.000905 0.364272 0.561777 cg03236184 1.901193 7.83E−05 0.438936 0.706127 Ras association domain family RASSF1 Homo sapiens cg02930432 1.590468 2.75E−09 0.197452 0.462608
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